Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite ...the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS-MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature.
Aims. We aim at constraining evolutionary models at low mass and young ages by identifying interesting transiting system members of the nearest OB association to the Sun, Upper Scorpius (USco), which ...has been targeted by the Kepler mission. Methods. We produced light curves for M-dwarf members of the USco region that has been surveyed during the second campaign of the Kepler K2 mission. We identified by eye a transiting system, USco J161630.68−251220.1 (=EPIC 203710387) with a combined spectral type of M5.25, whose photometric, astrometric, and spectroscopic properties makes it a member of USco. We conducted an extensive photometric and spectroscopic follow-up of this transiting system with a suite of telescopes and instruments to characterise the properties of each component of the system. Results. We calculated a transit duration of about 2.42 h that occurs every 2.88 days with a slight difference in transit depth and phase between the two components. We estimated a mass ratio of 0.922 ± 0.015 from the semi-amplitudes of the radial velocity curves for each component. We derived masses of 0.091 ± 0.005M⊙ and 0.084 ± 0.004M⊙, radii of 0.388 ± 0.008R⊙ and 0.380 ± 0.008R⊙, luminosities of log (L/L⊙) = −2.020-0.121+0.099 dex and −2.032-0.121+0.099 dex, and effective temperatures of 2901-172+199 K and 2908-172+199 K for the primary and secondary, respectively. Conclusions. We present a complete photometric and radial velocity characterisation of the least massive double-line eclipsing binary system in the young USco association with two components close to the stellar/substellar limit. This system falls in a gap between the least massive eclipsing binaries in the low-mass and substellar regimes at young ages and represents an important addition to constraining evolutionary models at young ages.
Previous studies have shown the existence of an acute phase response in dogs with heartworm (Dirofilaria immitis), probably caused by the vascular inflammation that occurs during the pathogenesis of ...this disease. In addition, it has been seen that this acute phase response persists after finishing treatment, especially in dogs with pulmonary hypertension (PH). Furthermore, echocardiographic studies have shown that PH and endarteritis appear to persist for at least 10 months after completion of adulticide treatment, suggesting that the vascular changes in these dogs may not be reversible. Therefore, the objective of this study was to evaluate the serum concentrations of different positive acute phase proteins (APP) C reactive-protein (CRP), haptoglobin and ferritin and negative APP (albumin and paraoxonase-1 (PON-1)), and the usefulness of the endothelin-1 (ET-1) and adiponectin, in dogs infected by D. immitis to evaluate their usefulness as diagnostic biomarkers of vascular damage and PH and their progression throughout therapy up to 7 months after the end of adulticide treatment. Twenty-five heartworm-infected dogs received adulticide treatment, and serum measurements were performed on the day of diagnosis (day 0), day of discharge (day 90), and 6 months after discharge (day 270). In addition, presence or absence of PH was also echocardiographically determined using the Right Pulmonary Artery Distensibility Index. PH was present in 44% of the dogs on day 0 and day 90, and in 48% of dogs on day 270. Alterations were observed in the concentrations of all APP throughout the study, persisting the alterations in PON-1 and ferritin on day 270. Depending on the presence or absence of PH, CRP showed significant differences throughout the study, as did ET-1. On the other hand, adiponectin did not show variations throughout the study, so it did not seem a useful marker in this disease. These results could reflect the possible persistence of vascular inflammation up to 7 months after finishing treatment, whether or not there was PH, and consolidate the study of APP as useful markers in heartworm disease. Moreover, persistent PH could be the consequent clinical manifestation in dogs with more severe vascular alterations so the study of APP, especially CRP, and ET-1 could be especially advantageous in these patients in the early evaluation of the disease, as well as for the determination of disease severity, monitoring therapeutic responses, and predicting outcomes.
•An acute phase response persists in dogs with heartworm 7 months after treatment.•C reactive-protein was higher in dogs with pulmonary hypertension after treatment.•Endothelin-1 is a good biomarker for pulmonary hypertension, before and after treatment.•The results could reflect a persistence of vascular inflammation 7 months after treatment.
El objetivo de este trabajo es hacer una selección de las publicaciones periódicas básicas que una biblioteca especializada debe contener, en este caso en el área de Biomedicina. La metodología ...empleada es aplicable a publicaciones periódicas de cualquier campo temático y consistió en el acceso, consulta, comparación y análisis de las distintas bases de datos especializadas, tanto en soporte CD-ROM, como impreso o magnético. Se extrajo una lista de títulos indizados por estas bases de datos y se procedió a la comparación, confrontación y análisis de los títulos obtenidos. La selección de revistas obtenida se comparó con la del Journal Citation Reports para analizar en qué medida se aproximan ambos listados.
Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors ...the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson's chi-squared or Fisher's exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann-Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples.
Abstract
JAXA's upcoming MMX (Martian Moons eXploration) mission will deliver a small rover to Phobos, to explore its surface complementary to the MMX orbiter and the sample return lander. On board ...this rover is a Raman spectrometer, the RAX Instrument (RAman Spectrometer for MMX), a payload to science. RAX has been designed for being capable to analyze the mineral composition of the Phobos' surface, in order to help reveal the nature and distribution of materials on the surface and ultimately the origin and evolution of the moon. Attached to MMX spacecraft, with direct view from the RAX instrument, a polyethylene terephthalate (PET) target will be placed for on‐ground and during cruise, spectral instrument performances verification, before the MMX rover is released and dropped to the Phobos surface for developing its scientific tasks. A novel deuterated PET material was proposed as verification target (VT) to check the spectral instrument performances. INTA‐CAB developed, manufactured and qualified for the MMX‐RAX space mission, 13 mm diameter and 2‐mm thick pellets of this material, which incorporates two relevant improvement characteristics: reduction in fluorescence and additional Raman bands with regard to ordinary PET used with this purpose. The material was selected as RAX VT and delivered to DLR for performance tests and later integration into the MMX rover together with the RAX flight model. The RAX VT will be critical to check the instrument performances during the several months cruise phase after launch and just before its landing on Phobos surface. This paper reports the development and characterization of the deuterated PET.
INTRODUCTIONWe analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission.PATIENTS AND METHODSWe conducted a retrospective, ...observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020.RESULTSWe included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation SD) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P=.002; 95%CI: 4.032-6.022; OR: 3,594).CONCLUSIONSSevere COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.
To determine the prevalence of hypotension and associated factors in hypertensive patients treated in the Primary Care setting.
A cross-sectional, descriptive, and multicentre study was conducted ...with a total of 2635 general practitioners consecutively including 12,961 hypertensive patients treated in a Primary Care setting in Spain. An analysis was performed on the variables of age, gender, weight, height, body mass index, waist circumference, cardiovascular risk factors (diabetes, dyslipidaemia, smoking, obesity, sedentary lifestyle), fasting plasma glucose, complete lipid profile, as well as the presence of target organ damage (left ventricular hypertrophy, microalbuminuria, carotid atherosclerosis) and associated clinical conditions. Hypotension was defined as a systolic blood pressure less than 110mmHg or a diastolic blood pressure less than 70mmHg. A multivariate analysis was performed to determine the variables associated with the presence of hypotension.
The mean age was 66.2 years, and 51.7% of patients were women. The mean time of onset of hypertension was 9.1 years. A total of 13.1% of patients (95% confidence interval 12.4-13.6%) had hypotension, 95% of whom had low diastolic blood pressure. The prevalence of hypotension was higher in elderly patients (25.7%) and in those individuals with coronary heart disease (22.6%). The variables associated with the presence of hypotension included a history of cardiovascular disease, being treated with at least 3 antihypertensive drugs, diabetes, and age.
One out of 4-5 elderly patients, or those with cardiovascular disease, had hypotension. General practitioners should identify these patients in order to determine the causes and adjust treatment to avoid complications.
The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ...ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together.
To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR).
We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality ACM, cardiovascular mortality CVM, myocardial infarction MI, stroke and MACE) and of safety (major bleeding events MBE, major gastrointestinal bleeding events MGIBE, and intracranial and extracranial bleeding) were shown.
The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% SD±5.7), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% SD±3.3). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively.
The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM.
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